Effect of Captopril Treatment on Chronic Hypoxia Induced Pulmonary Vascular Remodeling in the Fawn-Hooded, Spraque-Dawley, and Brown-Norway Rat

Pulmonary vascular remodeling is one of the typical responses to chronic alveolar hypoxia in the rat model of pulmonary hypertension (PH). Neither the etiology nor the structural and functional consequences of this remodeling are well understood. It is known that chronic treatment with ACE inhibitors results in a reduction of lung perfusion pressures and vascular changes in hypoxic PH, but the effect of treatment with ACE inhibitors on arterial tree morphology and mechanical properties of the artery walls in the intact lung have not been examined. In addition to using standard hemodynamic analysis, we approach this problem with x-ray micro-CT imaging and measure the distensibility of pulmonary arteries (approximate range of 50 – 2000 um diameter) in rat lungs. We examine consequences of chronic hypoxic exposure (10% O2) with and without Captopril treatment in FH, SD and BN rats. The FH rat strain is known to possess a genetic susceptibility to PH whereas the BN strain is resistant to PH. An example of phenotypic divergence between the strains: isolated lung studies indicate differences in the baseline perfusion pressures. The pulmonary arterial-venous pressure differential is 11.3±0.45, 8.86±0.65, and 7.74±0.38 [mmHg±SE] for normoxia at a flow rate of 120 ml/(min•kg) in the FH, SD, and BN strain, respectively